The present invention relates to monoclonal antibodies specific for a cell receptor that binds human stem cell factor (hSCF), as well as pharmaceutical compositions containing such monoclonal antibodies and uses of such monoclonal antibodies.
Stem Cell Factor (SCF) is a growth factor that stimulates the proliferation of pluripotent hematopoietic progenitor cells. It has been produced recombinantly in E. coli and various mammalian cells [Zsebo et al., Cell 63:195-212 (1990); and U.S. Patent applications Ser. Nos. 07/589,701, 07/573,616, and 07/537,198, filed Oct. 1, 1990, Aug. 24, 1990, and Jun. 11, 1990, respectively].
The proto-oncogene c-kit has recently been identified as the receptor for SCF [Zsebo et al., Cell 63:213-224 (1990)]. Prior to identification of c-kit as the ligand for SCF, the c-kit receptor was known to exist [Yarden et al., EMBO J. 6:3341-3351 (1987); Qiu et al., EMBO J. 7:1003-1011 (1988); Flanagan and Leder, Cell 63:185-194 (1990)].
Polyclonal antibodies directed against the murine c-kit have been reported [Cellular Biology 8:4896-4903 (1988)], but it is not known whether these antibodies will cross react with the human c-kit, whether they will block binding of SCF to its receptor, or whether they will affect cell growth. A polyclonal antibody raised against a human c-kit carboxy terminal peptide has also been reported [EMBO J. 6:3341-3351 (1987)], but these antibodies would not block SCF binding to the receptor. A monoclonal antibody that recognizes human SCF receptors has been reported [Lerner et al., Blood 76 (Suppl):295a, (1990); Ashman et al., Leukemia Res. 12:923-928 (1988); Cambaseri et al., Leukemia Res. 12:929-939 (1988); Gadd and Ashman, Leukemia Res. 11:1329-1336 (1985)].
Thus, until the existence of the present invention, the prior art has not been able to obtain a monoclonal antibody to the c-kit receptor with any expectation that such a monoclonal antibody would possess the ability to block the binding of the c-kit ligand, SCF.
This research is partially funded by the United Sates Government through National Institute of Health Grant P01-DK-31232 and the American Cancer Society Grant JFRA217.